FDA Approves Takeda’s Exkivity for Subset of NSCLC

The U.S. Food and Drug Administration granted accelerated approval to Takeda Pharmaceutical’s Exkivity for the treatment of certain adult patients with locally advanced or metastatic non-small cell lung cancer.

Photo: Teresa Bitetti, president, Global Oncology Business Unit, Takeda

The agency approved Exkivity for those non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor exon 20 insertion mutations as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.

The FDA simultaneously approved Thermo Fisher Scientific’s Oncomine Dx Target Test as an NGS companion diagnostic for Exkivity to identify NSCLC patients with EGFR Exon20 insertions. NGS testing is critical for these patients, as it can enable more accurate diagnoses compared to polymerase chain reaction testing, which detects less than 50 percent of EGFR Exon20 insertions.

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85 percent of the estimated 2.2 million new cases of lung cancer diagnosed each year worldwide, according to the World Health Organization. Patients with epidermal growth factor receptor (EGFR) Exon20 insertion+ NSCLC make up approximately 1-2 percent of patients with NSCLC, and the disease is more common in Asian populations compared to Western populations. This disease carries a worse prognosis than other EGFR mutations, as EGFR TKIs—which do not specifically target EGFR Exon20 insertions—and chemotherapy provide limited benefit for these patients.

Exkivity is a first-in-class, oral tyrosine kinase inhibitor (TKI) specifically designed to selectively target EGFR Exon20 insertion mutations. The FDA granted priority review and Breakthrough Therapy, Fast Track, and Orphan Drug designations to Exkivity.

The accelerated approval was based on overall response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

“Patients with EGFR Exon20 insertion+ NSCLC have historically faced a unique set of challenges living with a very rare lung cancer that is not only underdiagnosed, but also lacking targeted treatment options that can improve response rates,” said Marcia Horn, executive director, Exon 20 Group at ICAN, International Cancer Advocacy Network. “As a patient advocate working with EGFR Exon20 insertion+ NSCLC patients and their families every day for nearly five years, I am thrilled to witness continued progress in the fight against this devastating disease and am grateful for the patients, families, healthcare professionals and scientists across the globe who contributed to the approval of this promising targeted therapy.”

The FDA approval is based on results from the platinum-pretreated population in the phase 1/2 trial of Exkivity, which consisted of 114 patients with EGFR Exon20 insertion+ NSCLC who received prior platinum-based therapy and were treated at the 160 mg dose. Results were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting from the phase 1/2 trial and demonstrated a confirmed ORR of 28 percent per independent review committee (IRC) (35 percent per investigator) as well as a median DoR of 17.5 months per IRC, a median overall survival (OS) of 24 months and a median progression-free survival (PFS) of 7.3 months per IRC.

The most common adverse reactions (>20 percent) were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain. The Exkivity Prescribing Information includes a boxed warning for QTc prolongation and Torsades de Pointes, and warnings and precautions for interstitial lung disease/pneumonitis, cardiac toxicity, and diarrhea.

The FDA review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence (OCE), which provides a framework for concurrent submission and review of oncology products among international partners. We look forward to continuing our work with regulatory agencies across the globe to bring mobocertinib to patients.

“The approval of Exkivity introduces a new and effective treatment option for patients with EGFR Exon20 insertion+ NSCLC, fulfilling an urgent need for this difficult-to-treat cancer,” said Teresa Bitetti, president, Global Oncology Business Unit, Takeda. “Exkivity is the first and only oral therapy specifically designed to target EGFR Exon20 insertions, and we are particularly encouraged by the duration of the responses observed with a median of approximately 1.5 years.”

Author: Rare Daily Staff